摘要：Objectives. We sought to estimate the risk for autism associated with maternal and paternal age across successive birth cohorts. Methods. We linked birth records and autism diagnostic records from the California Department of Developmental Services for children born in California between 1992 and 2000 to calculate the risk associated with maternal and paternal age for each birth cohort as well as for the pooled data. Results. The categorical risks associated with maternal age over 40 years ranged from a high of 1.84 (95% confidence interval [CI] = 1.37, 2.47) to a low of 1.27 (95% CI = 0.95, 1.69). The risk associated with paternal age ranged from 1.29 (95% CI = 1.03, 1.6) to 1.71 (95% CI = 1.41, 2.08). Conclusions. Pooling data across multiple birth cohorts inflates the risk associated with paternal age. Analyses that do not suffer from problems produced by pooling across birth cohorts demonstrated that advanced maternal age, rather than paternal age, may pose greater risk. Future research examining parental age as a risk factor must be careful to avoid the paradoxes that can arise from pooling data, particularly during periods of social demographic change. The prevalence of autism, a developmental disorder characterized by serious impairments in social interaction and language development as well as stereotyped and repetitive behaviors, has increased dramatically over the past 2 decades from approximately 4 to 40 cases per 10 000. 1 The cause of the increase is unknown, as is the etiology of autism. Evidence from twin studies suggests that autism is likely a genetic disorder. 2 – 4 However, genetic causes for the vast majority of autism cases have not yet been identified through molecular genetic research. 5 In addition, dozens of previous studies have identified a wide range of perinatal and parental risk factors. 6 Despite these studies, our understanding of even the most basic of these factors, parental age, is muddled. Previous studies examining the association between parental age and autism have yielded contradictory results. With respect to mothers, 5 of the 11 studies that examined the risk associated with maternal age and autism spectrum disorders reported an increase in risk after adjustment for other confounding factors. 7 – 11 Six studies did not identify significant elevated risk. 12 – 17 Paternal age has also been associated with autism. Four of 7 studies found an association between paternal age and autism. 7 , 10 , 13 , 17 However, there is wide variability in the reported risk, spanning from no association 8 , 12 to an almost 6-fold increase when paternal age exceeds 40 years. 17 (These previous studies are summarized in an appendix that is available as a supplement to the online version of this article at http://www.ajph.org .) With the exception of a recent study that examined the birth cohort of 1994 in 10 US States, 7 all previous studies have pooled observations across several birth cohorts; in fact, it is not uncommon for studies to pool data from individuals who are born 10 to 20 years apart. 11 , 13 – 16 However, paternal age, and particularly the proportion of the paternal population over 40 years of age, increased rapidly during this period. We provide the first investigation into changes in risk factors associated with autism across successive birth cohorts. We aimed to estimate the risk for autism associated with maternal and paternal age across successive birth cohorts to gain insight into possible sources of discrepancies in previous studies.
